Histamine-induced Wheal Research Articles

Effect of the H 2-antagonist cimetidine on the pharmacokinetics and pharmacodynamics of the H 1-antagonists hydroxyzine and cetirizine in patients with chronic urticaria

Background: Concomitant administration of an H 1-receptor antagonist with an H 2-receptor antagonist may enhance the wheal and flare suppression produced by the H 1-antagonist. This synergism may be due, at least in part, to a pharmacokinetic effect. Methods: In a randomized, double-blind, parallel-group study in 16 patients with chronic urticaria, we investigated the pharmacokinetics and suppressive effect on the histamine-induced wheal and flare of a single dose of hydroxyzine 25 mg or cetirizine 10 mg, given before and after treatment with cimetidine 600 mg every 12 hours for 10 days. Results: When hydroxyzine was administered with cimetidine, the partial hydroxyzine area under the curve increased significantly ( p < 0.05) to 303 ± 92 ng/ml/hr from 227 ± 77 ng/ml/hr after administration of hydroxyzine alone, and the concentration of cetirizine arising from hydroxyzine was lower. When hydroxyzine was given with cimetidine, wheal and flare suppression increased compared with when hydroxyzine was given alone, but the differences were not statistically significant (p > 0.05). When cetirizine was administered with cimetidine, the pharmacokinetics of cetirizine did not change significantly, and no enhancement of wheal and flare suppression was observed. Conclusions: In this study co-administration of hydroxyzine with cimetidine resulted in significantly increased serum hydroxyzine concentrations and increased wheal and flare suppression, thus confirming the rationale for a trial of concomitant administration of these medications in some patients with chronic urticaria unresponsive to treatment with an H 1-antagonist alone. We found no therapeutic rationale for co-administration of cetirizine with cimetidine in urticaria treatment. These medications may be co-administered safely without fear of medication interaction. (J A LLERGY C LIN I MMUNOL 1995;95:685-93.)

Reliability of skin prick tests during terfenadine treatment in adults with pollen rhinitis

The variation in skin prick test (SPT) results was evaluated clinically during terfenadine treatment in 39 adult patients with pollen rhinitis. A change in the perceived state of the patient as regards sensitization to a specific pollen allergen or atopic constitution was judged to be clinically important. A randomized, double-blind, crossover design was used, comprising 2 weeks on terfenadine 120 mg once a day and 2 weeks on placebo. SPT for two pollen allergens and histamine (10 mg/ml) were evaluated at the start of the study and at the end of each period. When SPT was used as a discovery test and liberal definitions were applied, predictive values for a positive test were 100%. 1-Sensitivity ranged between 10 and 54% with substantially lower values when a histamine wheal reaction was noted. The inhibitory effect of terfenadine was detectable 2 weeks after withdrawal as a reduction in the median of the mean diameter for the histamine-induced wheal response of 1 mm (0-1.5). The data implied that a positive SPT is reliable when liberal definitions are adopted for sensitization and atopy; a negative SPT is presumably reliable when the measurement artifact is considered and the wheal reaction to histamine is detectable.

Benefit/risk ratio of the antihistamines (H 1-receptor antagonists) terfenadine and chlorpheniramine in children

There are few objective studies of the benefit/risk ratio of H1-receptor antagonists in children. We hypothesized that terfenadine would provide as effective peripheral H1 blockade as chlorpheniramine in young patients, but would cause less central nervous system dysfunction. We tested this hypothesis with epicutaneous histamine tests to monitor peripheral H1 blockade, P300-event-related potentials as a measure of cognitive processing, and a visual analog scale for somnolence, in a double-blind, single-dose, placebo-controlled, three-way crossover study in 15 children with allergic rhinitis (mean age, 8.5 +/- 1.4 years). On 3 different days the children received terfenadine, 60 mg, chlorpheniramine, 4 mg, or placebo; the tests were performed before and 2 to 2 1/2 hours after dosing. Both terfenadine and chlorpheniramine suppressed the histamine-induced wheal and flare compared with baseline and with placebo; terfenadine was significantly more effective (p < 0.05). Terfenadine did not increase the latency of P300-event-related potentials at the parietal (Pz) or frontal (Fz) scalp electrodes compared with baseline, in contrast to chlorpheniramine and placebo, which did increase P300 latency. Terfenadine and placebo did not increase somnolence compared with baseline, but chlorpheniramine did. In children, as previously documented in adults, terfenadine has a more favorable benefit/risk ratio than chlorpheniramine, as shown by production of significantly greater peripheral histamine blockade and significantly less central nervous system dysfunction.

Effect of the H2-receptor antagonist cimetidine, on the pharmacokinetics and pharmacodynamics of the H1-receptor antagonists hydroxyzine and cetirizine in rabbits.

The effects of coadministration of the H2-receptor antagonist cimetidine on the pharmacokinetics and pharmacodynamics of the H1-receptor antagonists hydroxyzine and cetirizine were studied in rabbits. A single dose of hydroxyzine, 10 mg (Experiment A), or cetirizine, 10 mg (Experiment B), was given intravenously on three occasions: 2 weeks before cimetidine administration, after cimetidine, 100 mg/kg, had been given every 12 hr for 1 week, and 2 weeks after the cimetidine was discontinued. Serum concentrations of hydroxyzine and cetirizine, the active metabolite of hydroxyzine arising in vivo (Experiment A), or cetirizine (Experiment B) were measured by HPLC. The pharmacologic effects of hydroxyzine and cetirizine were monitored by measuring the suppression of histamine-induced wheals, using an IBM-PC and digitizer. The hydroxyzine and cetirizine half-life and AUC0-->infinity values were significantly increased and the systemic clearance rates were significantly decreased in the presence of cimetidine. Similar results were obtained when cetirizine was administered de novo. Wheal suppression produced by hydroxyzine or cetirizine was increased and prolonged in the presence of cimetidine. The synergism observed between hydroxyzine or cetirizine and cimetidine in suppression of the histamine-induced cutaneous response may be due to a pharmacokinetic interaction.

Cetirizine Pharmacokinetics and Pharmacodynamics in Primary Biliary Cirrhosis

The new H1-receptor antagonist, cetirizine, is eliminated primarily unchanged by renal excretion and is thus potentially useful for relief of pruritus in patients with hepatic dysfunction, in whom many H1-receptor antagonists are contraindicated. The authors studied the elimination of cetirizine in six patients with primary biliary cirrhosis. In contrast to data obtained in healthy adults with normal hepatic function reported in the medical literature, they found that the mean serum elimination half-life value of cetirizine, 13.8 +/- 1.8 hours, was longer, and the mean clearance rate, 0.44 +/- 0.10 mL/min/kg, was lower (P < .05). The mean peak serum cetirizine concentration, 498 +/- 118 ng/mL, was higher, the mean area under the curve, 6438 +/- 1621 ng/mL/hr, was larger, and the mean fraction of the dose excreted as unchanged cetirizine in the urine, .32 +/- .14, was lower (P < .05). The duration of action of cetirizine was prolonged, as evidenced by significant suppression of the histamine-induced wheal and flare for 48 and 72 hours, respectively, after a single dose. Cetirizine elimination was impaired in patients with hepatic dysfunction.

Histamine H2-Receptor Plays Only a Minor Role in Histamine-Induced Wheal Response in the Squirrel Monkey and Guinea Pig

We examined the contribution of the histamine H2-receptor to the histamine-induced wheal response in squirrel monkeys and guinea pigs. Intradermal injection of histamine, 2-pyridylethylamine (a selective H1-agonist), and dimaprit (a selective H2-agonist) dose-dependently induced the wheal response in squirrel monkeys and guinea pigs, although the reaction to dimaprit was much weaker than that to the other agonists. Chlorpheniramine dose-dependently depressed the wheal response in squirrel monkeys and guinea pigs at doses of 0.03-1 mg/kg and 0.03-3 mg/kg, p.o., respectively. However, famotidine, ranitidine and cimetidine had no effect at doses up to 30, 100 and 300 mg/kg, p.o. in guinea pigs and up to 1, 10 and 400 mg/kg, p.o. in squirrel monkeys, respectively. Cimetidine (3-300 mg/kg, p.o.) dose-dependently potentiated the inhibitory effects of chlorpheniramine (0.1 mg/kg, p.o.) in guinea pigs, but had no effects in squirrel monkeys. Famotidine and ranitidine did not alter the response to chlorpheniramine in either animal. These results suggest that the histamine H2-receptor plays only a minor role in the histamine-induced wheal response in squirrel monkeys and guinea pigs.

Comparison of the central and peripheral antihistamine effects of dimethindene maleate (Fenistil®) and its enantiomers

The H1 histamine receptor antagonist activity and sedative effects of dimethindene maleate racemate (DIM +/−) (FENISTIL®) and the individual enantiomers (DIM+ and DIM−) were monitored in parallel in a double-blind, placebo-controlled, cross-over study in 9 healthy subjects. Peripheral antihistamine activity (histamine-induced wheal and flare planimetry) and central effects (electroencephalography (EEG) and self-evaluation on a visual analogue scale (SEVS)) were measured after oral administration of a single dose of DIM+/− (4 mg), DIM+ (2 mg), DIM− (2 mg) and placebo.

Cetirizine, Oxatomide, Ketotifen and Placebo

At 1-week intervals, 12 healthy volunteers received oral cetirizine 10mg, oxatomide 30mg, ketotifen 1mg or placebo under randomised double-blind crossover conditions. Wheal and flare were induced by skin prick tests using histamine 100 and 500 g/L before, and 4, 8 and 24 hours after, drug ingestion. At each session volunteers recorded levels of pruritus and sedation on two 10cm visual analogue scales. Cetirizine was significantly more potent than oxatomide (p = 0.0001), ketotifen (p = 0.0002) or placebo (p = 0.0001) in the inhibition of wheals, with similar results for flare (p = 0.0007, 0.0001 and 0.0002, respectively). Relief from pruritus was significantly better with cetirizine than with oxatomide (p = 0.003) or ketotifen (p = 0.002). Cetirizine was slightly better than placebo in relieving pruritus, but this was not statistically significant. Oxatomide and ketotifen were clearly more sedative than cetirizine (p = 0.05 and p = 0.0006, respectively), which was not significantly different from placebo. In conclusion, cetirizine appeared to be better in reducing histamine-induced wheal, flare and pruritus compared with ketotifen and oxatomide, and had less sedative effect.

Histamine‐induced wheal, flare, and pruritus: Inhibition by cetirizine, terfenadine, and placebo

AbstractTwelve adult volunteers were enrolled in a four‐session, double‐blind, crossover, randomized study. On each session, two capsules were administered in the morning and contained the pulverised products of either placebo (P) + P, terfenadine (T) 60 (mg) +P, T 60 + T 60, or cetirizine (C) 10 + P. On the evening of each experimental day, two capsules were taken at 0800 pm either as P + P or as T 60 + P or as P + P, or as P + P. We thus have four groups called, respectively, placebo, terfenadine 60 bid, terfenadine 120, and cetirizine 10. Pricks (100 mg/ml histamine) were performed before drug intake and 5, 12, 17, and 24 hr after drug intake. Ten minutes after each prick, wheal areas were underlined and transfered onto a transparency to be measured later. One volunteer gave up the trial due to the appearance of a serious disease not related to the trial. Regarding initial wheals, cetirizine 10, terfenadine 60 bid, and terfenadine 120 significantly (P &lt; 0.01) reduced the wheal at H5, H12, H17, and H24 (except NS at H17 for T120). At H5, H12, and H17, cetirizine 10, terfenadine 60 bid, and terfenadine 120 were significantly more potent than P (P &lt; 0.03). At H24, only cetirizine 10 and terfenadine 60 bid were significantly more potent than placebo. Pairwise global comparison shows a significant difference (P = 0.03) in favour of cetirizine regarding terfenadine 120. Side effects under active drugs were not different from those under placebo.

52 Comparison of trough effects of five non-sedating antihistamines on histamine-induced wheal and flare reactions

52 Comparison of trough effects of five non-sedating antihistamines on histamine-induced wheal and flare reactions

Skin responses to intradermal histamine and leukotrienes C 4, D 4, and E 4 in patients with chronic idiopathic urticaria and in normal subjects

Mast cell inflammatory mediators, such as histamine, and newly formed compounds, such as the leukotrienes, cause wheal and flare when they are injected intradermally into normal subjects and may therefore play a role in the formation of urticaria. The effects of intradermal injections (50 microliters) of six different concentrations of histamine (range, 3.3 x 10(-4) to 3.3 x 10(-9) mol/L) and the leukotrienes C4, D4, and E4 (range, 2 x 10(-4) to 2 x 10(-9) mol/L) have been compared in 10 normal subjects and in 10 patients with chronic idiopathic urticaria. Wheal-and-flare sizes were measured at timed intervals up to 4 hours, and area under the curve for each response over time was calculated. There were no significant differences in leukotriene-induced responses between groups. Maximum sizes of histamine-induced wheal and flare were similar in each group of subjects. There were, however, significant increases in mean areas under the response curve of histamine wheal and flare in the patients with urticaria (wheal, p less than 0.001; flare, p less than 0.001; analysis of variance). These findings demonstrate a prolongation of skin responses to histamine in patients with urticaria and suggest an impaired clearance of histamine (or other vasoactive agents released by histamine) from the skin of these patients.

A double-blind, single-dose, crossover comparison of cetirizine, terfenadine, loratadine, astemizole, and chlorpheniramine versus placebo: Suppressive effects on histamine-induced wheals and flares during 24 hours in normal subjects

We objectively tested the relative antihistaminic effects of cetirizine, 10 mg; terfenadine, 120 mg; terfenadine, 60 mg; loratadine, 10 mg; astemizole, 10 mg; chlorpheniramine, 4 mg; and placebo in healthy, male volunteers, mean age 25 +/- 4 years, and mean weight, 73 +/- 9 kg. The wheal areas and flare areas produced by epicutaneous tests with histamine phosphate, 1 mg/ml, before ingestion of the H1-receptor antagonist or placebo, and afterward, at 0.3 and 0.7 hours, then hourly from 1 to 12 hours and at 24 hours, were traced at 10 minutes and measured with an IBM-PC digitizer and stereometric software. In this experimental model, the H1-receptor antagonists differed significantly with regard to time of onset of action, amount of suppression of the histamine-induced wheal and flare, and duration of action. The rank order was, from most effective to least effective, cetirizine, 10 mg; terfenadine, 120 mg; terfenadine, 60 mg; loratadine, 10 mg; astemizole, 10 mg; chlorpheniramine, 4 mg; and placebo.

Mast cell chymase potentiates histamine-induced wheal formation in the skin of ragweed-allergic dogs.

Skin mast cells release the neutral protease chymase along with histamine during degranulation. To test the hypothesis that chymase modulates histamine-induced plasma extravasation, we measured wheal formation following intradermal injection of purified mast cell chymase and histamine into the skin of ragweed-allergic dogs. We found that chymase greatly augments histamine-induced wheal formation. The magnitude of the potentiating effect increases with increasing doses of chymase and becomes maximal approximately 30 min after administration. Injection of chymase without histamine does not evoke wheal formation. The chymase potentiation of histamine-induced skin responses is prevented completely by pretreatment with the H1-receptor antagonist pyrilamine, and is prevented by inactivation of chymase with soybean trypsin inhibitor, suggesting that both histamine and preserved catalytic activity are required for the effects of chymase. To examine the effects of histamine and chymase released in situ in further experiments, we measured wheal size following local degranulation of mast cells by intradermal injection of ragweed antigen or compound 48/80. We found that pretreatment with either soybean trypsin inhibitor or pyrilamine markedly reduces ragweed antigen- or 48/80-induced wheal formation, supporting the results obtained by injection of exogenous chymase and histamine. These findings suggest a novel and important proinflammatory role for chymase in modulating the effects of histamine on vascular permeability during mast cell activation.

Inhibition of anti‐IgE induced skin response in normals by formoterol, a new β2 adrenoceptor agonist, and terbutaline

The intention of the present study was to compare formoterol and terbutaline regarding ability to inhibit immediate wheal and flare responses (WFR) to anti-human IgE with focus on the duration of anti-WFR action. Formoterol is a novel beta 2-adrenergic agonist with a prolonged duration of bronchodilation capacity after inhalation. The drugs injected intradermally 2 min prior to challenge with anti-IgE in volunteers produced a dose-dependent inhibition of the WFR in the range 1pg-100ng (formoterol) and 1ng-1 microgram (terbutaline). Formoterol was 70 times (flare) and 25 times (wheal) more potent (ID40) than terbutaline on a weight basis. The duration of the anti-WFR action for formoterol, injected in a 25 times lower dose than terbutaline, was significantly longer, namely greater than 24 h versus 8 h for terbutaline. The histamine-induced wheal reaction was attenuated by 15% and 25% by terbutaline and formoterol, respectively. The results indicate a higher beta 2-receptor activity for formoterol with respect to inhibition of IgE-dependent mast cell mediator release in addition to an anti-leak effect exerted by both drugs. The prolonged duration of antagonistic effect by formoterol on the WFR to anti-IgE might be due to the lipophilic property of the drug, with an expected higher retention of formoterol at the target tissue compared with the more hydrophilic compound terbutaline.

A quantitative comparison of the effect of local analgesics on argon laser induced cutaneous pain and on histamine induced wheal, flare and itch.

A quantitative comparison was made of the effect of infiltration of local analgesics and topical analgesic cream (EMLA) on laser-induced pain and histamine-induced wheal, flare and itch. Wheal and flare were quantified by planimetry and analgesia was quantified by the pricking pain threshold to argon laser stimulation. The intensity of histamine-induced itch was scored on a 4-point scale. Local analgesics had no effect on the wheal area. The flare reaction was abolished by infiltrating lignocaine, and gradually inhibited by increased application times of EMLA. Itch was abolished after local lignocaine infiltration, but not significantly reduced after EMLA cream applied for less than 120 min, although the skin was anaesthetized to laser-induced pain. The reduction of flare area correlated to the level of analgesia, which may therefore reflect the cutaneous responsiveness to neurogenic inflammation. It is suggested that itch and pricking pain are mediated by different populations of nerve fibres, as itch can be evoked even when the sensation of pricking pain is abolished. Surgery, skin prick tests and other traumatic procedures should therefore be performed under local anaesthesia to reduce neurogenic inflammation.

Cetirizine: A pharmacokinetic and pharmacodynamic evaluation in children with seasonal allergic rhinitis

In a double-blind, randomized, parallel-group 5-week study, cetirizine, 5 mg or 10 mg daily, was ingested by 10 and nine children, respectively. Cetirizine was rapidly absorbed with mean peak cetirizine concentrations of 427.6 ± SD, 144.2 ng/ml. 1.4 ± 1.1 hours after the 5 mg dose, and 978.4 ± 340.6 ng/ml, 0.8 ± 0.4 hours after the 10 mg dose. The dose-independent serum-elimination half-life of cetirizine was 7.1 ± 1.6 hours after cetirizine, 5 mg, and 69 ± 1.6 hours after cetirizine, 10 mg. Urinary excretion of unchanged cetirizine during 24 hours after the initial dose of cetirizine, 5 mg, was 40 ± 15%, and after cetirizine, 10 mg, it was 39 ± 14%. The mean histamine-induced wheal-and-flare areas were significantly suppressed from 1 to 24 hours after the first dose of cetirizine, 5 mg, and from 1 2 to 24 hours after the first dose of cetirizine, 10 mg, compared to the mean predose wheal-and-flare areas ( p < 0.01). During daily dosing with cetirizine, 5 mg or 10 mg at bedtime for 35 days, serum cetirizine concentrations and suppression of histamine-induced wheals and flares were monitored every 7 days, 12 hours after the cetirizine dose. The mean serum cetirizine concentrations remained relatively stable during this time, and the mean wheal-and-flare areas remained significantly suppressed ( p < 0.01) compared to baseline wheal-and-flare areas measured before the first dose of cetirizine. The symptoms and signs of allergic rhinitis were suppressed throughout the study by cetirizine, 5 mg and 10 mg. No sedation, dry mouth, or other adverse effects were reported at any time. Cetirizine is a potent, new H 1-receptor antagonist without central nervous system or anticholinergic activity. No evidence of subsensitivity to cetirizine was found during 5 weeks of treatment.

Lack of subsensitivity to terfenadine during long-term terfenadine treatment

Eleven healthy male volunteers ingested térfenadine, 60 mg, every 12 hours for 56 days. Compliance was monitored strictly throughout the study. Before the first terfenadine dose on day 0, and 12 hours after the evening terfenadine dose every seventh day and on randomly selected “unscheduled” days, wheal-and-flare areas were measured after intradermal injections of 0.01 ml of histamine phosphate (1.0 mg/ml and 0.1 mg/ml). On days 0, 28, and 56, six volunteers had skin tests hourly for 12 hours after the morning terfenadine dose. On all study days, serum terfenadine metabolite I concentrations were measured each time histamine skin tests were performed. On days 7, 14, 21, 28; 35, 42, 49, and 56, the mean areas of the histamine-induced wheals did not differ significantly from each other but were significantly decreased compared to the mean wheal area on day 0 ( p < 0.01). On these days, the mean areas of the histamine- induced flares also did not differ significantly from each other but remained significantly suppressed compared to the mean flare areas on day 0 ( p < 0.01). Wheal-and-flare suppression was noted in all unscheduled histamine skin tests performed 12 hours after the evening terfenadine dose. In the subgroup of volunteers who had hourly tests, on day 0, the mean wheal-and-flare areas were significantly suppressed from 2 to 12 hours after the dose, with maximal wheal suppression occurring at 5 hours ( p < 0.05) and maximal flare suppression occurring from 3 to 9 hours ( p < 0.01). On day 28 in the subgroup, the mean wheal area was significantly larger 12 hours after the dose than before the dose or at any other time ( p < 0.01), but the mean flare areas did not differ significantly at any time ( p = 0.01). On day 56 in the subgroup, the mean wheal areas did not differ significantly from before the dose to 12 hours after the dose, nor did the mean flare areas differ significantly at any time ( p = 0.01). The mean serum concentration of terfenadine metabolite 112 hours after the evening dose did , not differ significantly on days 7, 14,21, 28, 35, 42, 49,adn 56 ( p = 0.01). Unscheduled serum terfenadine metabolite I concentrations measured 12 hours after the dose provided additional confirmation of compliance. In the subgroup, the mean serum elimination half-life value and the mean area under the serum concentration versus time curve of terfenadine metabolite I did not differ significantly on day 0, day 28, or day 56 ( p = 0.01). We conclude that subsensitivity to the antihistaminic effect of terfenadine did not develop during 56 days in compliant subjects, as evidenced by continued suppression of the histamine-induced wheals and flares. Also, the pharmacokinetics of terfenadine metabolite 1 remained unchanged after 56 days of terfenadine treatment.

The pharmacokinetics and pharmacodynamics of terfenadine in children

The pharmacokinetics and pharmacodynamics of terfenadine were studied in 13 children with allergic rhinitis, mean age 7.45 +/- 0.54 SEM years. Serum concentrations of the active carboxylic acid metabolite of terfenadine (terfenadine metabolite I) were measured before and hourly for 8 hours after administration of a single dose of terfenadine suspension. The mean maximum serum concentration of terfenadine metabolite I, 242 +/- 28 ng/ml, occurred at 2.3 +/- 0.2 hours; the mean serum half-life value was 2.0 +/- 0.1 hours. Wheals and flares after epicutaneous tests with histamine phosphate, 1.0 mg/ml and 0.2 mg/ml, were significantly suppressed from 1 to 8 hours after the terfenadine dose compared to predose values. Maximum wheal suppression occurred at from 3 to 6 hours. Itching was completely suppressed for 8 hours. No serious adverse effects occurred. Terfenadine in children appears to be well absorbed, and its carboxylic acid metabolite has a short serum elimination half-life. The duration of its suppressive effect on the histamine-induced wheal and flare greatly exceeds that expected from consideration of serum terfenadine metabolite I concentrations.

Neutrophils are involved in the increased vascular permeability produced by activated complement in man.

To investigate the role of neutrophils in complement-induced changes in vascular permeability, skin wheal and flare responses to intradermal injection of autologous activated serum complement were measured in normal and neutropenic subjects. In normal subjects, responses were dose-dependent and were abolished by removal of C5 from serum. Biopsy of a wheal revealed neutrophils adherent to vascular endothelium. In neutropenic subjects (neutrophil count less than 0.5 X 10(9)/l), responses to complement-activated serum or a low molecular weight fraction from it were significantly reduced. This could not be accounted for by a reduction in concentration of C5 conversion products. In one subject with chronic granulomatous disease a normal response was produced. Local injection of the anti-histamine (H1) drug clemastine produced only partial inhibition of responses, while almost totally abolishing histamine-induced wheals. Systemic anti-inflammatory drugs had no effect. The data suggest that the microvascular response to activated complement in man is at least partly due to an interaction between C5 fragments and neutrophils.

Comparison of the suppressive effect of astemizole, terfenadine, and hydroxyzine on histamine-induced wheals and flares in humans

Thirty-two healthy volunteers completed a 14-day, double-blind, noncrossover study comparing the efficacy and adverse effects of astemizole, terfenadine, and hydroxyzine. The subjects received either astemizole (load), 30 mg once daily for 1 week and then 10 mg once daily for 1 week, or astemizole (no load), 10 mg once daily for 2 weeks, or terfenadine, 60 mg twice daily for 2 weeks, or hydroxyzine, 50 mg once daily for 2 weeks. Before and on days 7 and 14 of treatment, five intradermal tests with various amounts of histamine phosphate (range 0.3 to 40 micrograms) were performed. Wheal-and-flare responses were traced, and the areas were computed by use of a graphics tablet. All four H1-receptor antagonist treatment regimens were equally effective in reducing the flare response to histamine. Astemizole (load) and hydroxyzine were significantly more effective than terfenadine and astemizole (no load) in reducing wheal size. The incidence of adverse effects, including sedation, was low overall and lowest in the astemizole (no load) and terfenadine groups, although this difference was not statistically significant.